Ring Formation by 5-endo-dig Cyclization

Knight, David W.

doi:10.1016/bs.aihch.2018.09.004

Cited by 10 publications

(5 citation statements)

References 515 publications

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“…With several enyne-substituted DKP aldol condensation products 10a – e in hand, we explored conditions that could promote the desired pyrrole annulation. Although protic acids ( e.g ., CSA) failed to initiate the desired C–N bond formation, we found that Lewis acid catalysis, in particular cationic gold complexes at elevated temperatures, efficiently led to 5-endo cyclization and pyrrole formation to give products 11a – e . For example, the n -butyl-substituted derivative 11a was prepared in 68% yield through the exposure of the aldol condensation precursor 10a to Au(PPh) 3 Cl and AgBF 4 (5 mol % each) in THF at 66 °C.…”

Section: Resultsmentioning

confidence: 91%

Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine

et al. 2020

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This study reveals an alternative sequence for the synthesis of compounds that contain the pyrrolodiketopiperazine structural motif. Starting with a diketopiperazine precursor, a mild aldol condensation precedes pyrrole annulation and bicyclic ring fusion. The derived intermediate aldol condensation products, which bear either a protected carbonyl or a functionalized alkyne, can be cyclized to the pyrrolodiketopiperazine by protic or gold Lewis acid catalysis.

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Section: Resultsmentioning

confidence: 91%

Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine

et al. 2020

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“…Cationic Au-complex B was used for ether cyclization of four substrates 2a – d . The first attempt at cyclization using 2a with catalytic B (20 mol %) in CH 2 Cl 2 did not provide the desired 6-membered ether, but instead furan 24a in 70% yield plausibly by 5- endo - dig cyclization of the C10-hydroxy group . On the other hand, the desired 6- exo - dig cyclizations of 2b and 2c provided only 6-membered ethers 24b and 24c , respectively.…”

Section: Resultsmentioning

confidence: 98%

“…The first attempt at cyclization using 2a with catalytic B (20 mol %) in CH 2 Cl 2 did not provide the desired 6-membered ether, but instead furan 24a in 70% yield plausibly by 5-endo-dig cyclization of the C10-hydroxy group. 15 On the other hand, the desired 6-exo-dig cyclizations of 2b and 2c provided only 6-membered ethers 24b and 24c, respectively. In sharp contrast, the same reaction conditions using acetonide 2d led to extensive 7-endo-dig cyclization to afford 24d.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Synthesis of Macrolactone Core of ent-Formosalide A via Regioselective Ether Cyclization

Mozumi,

Fukaya,

Ito

et al. 2024

J. Org. Chem.

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Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate Prorocentrum sp, whose structure is characterized by functionalized 5-and 6-membered ether rings embedded in the macrolactone and an all cis-tetraene side chain. Here, we report the synthesis of the macrolactone core of entformosalide A. Our approach is highlighted by the Au-mediated 6exo-dig cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner. Control experiments demonstrated that the acyclic protecting group of the C9,C10-diol was crucial for the desired 6-exo-dig cyclization. Theoretical studies were performed focusing on structural component analysis, which suggested that the C8−C9−C10-C11 dihedral angle induced by the protecting group controlled the regioselectivity. An additional 6 steps including Shiina macrolactone formation from the 6-membered ether ring completed the synthesis of the macrolactone core of ent-formosalide A.

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“…S10), which is a precursor to a 5-endo-dig ring closure that closes the D-ring. While this is considered to be a favorable ring closure per Baldwin’s rules and known to form butenolide rings 36 , the PMF profile for the formation of D-ring-H247 from CLIM indicates that there is a ∼ 90 kcal/mol barrier to forming the precursor. Thus, the D-ring-H247 modification is more likely to occur via a concerted mechanism from the Open D-S97 species since the free energy barrier is lower, at ∼ 38 kcal/mol.…”

Section: Discussionmentioning

confidence: 99%

Multiple modes of substrate hydrolysis-induced covalent modification of strigolactone receptors

Chen

Shukla

2022

Preprint

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The strigolactone signaling pathway in plants is unconventional among plant hormone signaling pathways in that the receptor also acts as an enzyme that hydrolyzes the strigolactone substrate. While the canonical view of strigolactone hydrolysis is that it occurs via a nucleophilic attack on the butenolide ring of strigolactone, an alternative Michael addition mechanism in which hydrolysis occurs via a nucleophilic attack on the enol-ether bridge has been proposed. Furthermore, while it is known that a hydrolysis-induced covalent modification to the receptor promotes strigolactone receptor activation, the nature of this covalent modification has been disputed. Here, we employ QM/MM string method simulations to determine the favored pathway of strigolactone hydrolysis and the nature of the covalent modification that acts as a promoter of strigolactone receptor activation. Our simulations show that strigolactone hydrolysis occurs via an acyl substitution pathway beginning with nucleophilic attack on the butenolide ring, which is well corroborated by previous experimental literature. Additionally, we show that multiple possible modes of covalent modifications to the catalytic residues by the butenolide ring are able to form and interconvert, reconciling several seemingly conflicting views on the hydrolysis-induced covalent modification to strigolactone receptors.

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Ring Formation by 5-endo-dig Cyclization

Cited by 10 publications

References 515 publications

Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine

Synthesis of Pyrrolopyrazinones by Construction of the Pyrrole Ring onto an Intact Diketopiperazine

Synthesis of Macrolactone Core of ent-Formosalide A via Regioselective Ether Cyclization

Multiple modes of substrate hydrolysis-induced covalent modification of strigolactone receptors

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